Novel anti-cd3 antibodies

Abstract

The present invention relates to novel antibodies that are specific for human CD3, in particular for the CD3ε domain.

1 . An antibody or functional fragment thereof, which is specific for human CD3, comprising:
 (a) a variable light chain domain,
 wherein the variable light chain domain comprises, from N-terminus to C-terminus, the regions LFW1-LCDR1-LFW2-LCDR2-LFW3-LCDR3-LFW4, wherein each LFW designates a light chain framework region, and each LCDR designates a light chain complementarity-determining region, and wherein said LCDRs together exhibit at least 84, 87, 90, 93 or 96 percent sequence identity, to the corresponding LCDRs of the VL sequence according to SEQ ID NO: 4; 
   and   (b) a variable heavy chain domain,
 wherein the variable heavy chain domain comprises, from N-terminus to C-terminus, the regions HFW1-HCDR1-HFW2-HCDR2-HFW3-HCDR3-HFW4, wherein each HFW designates a heavy chain framework region, and each HCDR designates a heavy chain complementarity-determining region, and wherein said HCDRs together exhibit at least 86, 89, 92, 94 or 97 percent sequence identity, to the corresponding HCDRs of the VH sequence according to SEQ ID NO: 8. 
   
     
     
         2 . The antibody or the functional fragment thereof according to  claim 1 , wherein said variable light chain domain is a chimeric light chain domain, comprising:
 (i) human Vκ1 framework regions LFW1 to LFW3, particularly Vκ1 framework regions LFW1 to LFW3 exhibiting at least 90, 91, 92, 93, 94, 95, 96, 97 or 98 percent sequence identity to the corresponding framework regions of the Vκ1 sequence according to SEQ ID NO: 4;   (ii) LFW4, which is selected from (a) a human Vλ germ line sequence for LFW4, particularly a Vλ germ line sequence selected from the SEQ ID NO: 17 and SEQ ID NO: 18, preferably SEQ ID NO: 17; and (b) a Vλ-based sequence, which has one or two mutations, particularly one mutation, compared to the closest human Vλ germ line sequence for LFW4 comprising an amino acid sequence selected from the SEQ ID NO: 17 and SEQ ID NO: 18, preferably SEQ ID NO: 17.   
     
     
         3 . The antibody or the functional fragment thereof according to  claim 1 , wherein said variable heavy chain domain is a VH3 heavy chain domain. 
     
     
         4 . The antibody or the functional fragment thereof according to  claim 1 , wherein said variable light chain domain exhibits at least 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% sequence identity to the amino acid sequence according to SEQ ID NO: 4, and/or wherein said variable heavy chain domain exhibits at least 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% sequence identity to the amino acid sequence according to SEQ ID NO: 8. 
     
     
         5 . The antibody or the functional fragment thereof according to  claim 1 , wherein said variable light chain domain comprises an Arginine or a Lysine at the light chain amino acid position 54 according to AHo numbering. 
     
     
         6 . The antibody or the functional fragment thereof according to  claim 1 , wherein said antibody or the functional fragment thereof is characterized, when tested in an scFv format, by an average midpoint of thermal unfolding temperature (Tm) exceeding at least 66° C. as determined by differential scanning fluorimetry. 
     
     
         7 . A multispecific polypeptide comprising the antibody or the functional fragment thereof according to  claim 1  and at least a second binding domain or a fragment thereof with specificity for a target different from 003. 
     
     
         8 . A pharmaceutical composition comprising the antibody or the functional fragment thereof of  claim 1  and a pharmaceutically acceptable carrier and/or excipient. 
     
     
         9 . A nucleic acid or a collection of nucleic acids encoding the antibody or the functional fragment thereof according to  claim 1 . 
     
     
         10 . A vector or a collection of vectors comprising the nucleic acid or the collection of nucleic acids of  claim 9 . 
     
     
         11 . A method for producing the antibody or the functional fragment thereof of  claim 1 , comprising the step of expressing a nucleic acid or a collection of nucleic acids encoding the antibody or the functional fragment thereof according to  claim 1 . 
     
     
         12 . A method of generating a multispecific construct, comprising the step of cloning, in one or more steps, one or more nucleic acids encoding the antibody or the functional fragment thereof according to  claim 1 , into a multispecific construct comprising a nucleic acid encoding at least a second binding domain or a fragment thereof, and, optionally, a nucleic acid encoding one or more additional binding domains or fragments thereof. 
     
     
         13 . The method of  claim 12 , wherein said second binding domain is a second antibody or a functional fragment thereof. 
     
     
         14 . A pharmaceutical composition comprising the multispecific polypeptide of  claim 7 , and a pharmaceutically acceptable carrier and/or excipient. 
     
     
         15 . A method of treating a disease, comprising the step of administering the multispecific polypeptide of  claim 7  to a patient in need thereof, wherein the disease is inflammatory disease, autoimmune disease or cancer, and wherein the second binding domain or fragment thereof is specific for IL32R or tumor associated antigen (TAA), respectively. 
     
     
         16 . A method of treating a disease, comprising the step of administering the pharmaceutical composition of  claim 14  to a patient in need thereof, wherein the disease is inflammatory disease, autoimmune disease or cancer, and wherein the second binding domain or fragment thereof is specific for IL32R or tumor associated antigen (TAA), respectively.